Name, Image, and Likeness Legislation: Who's Benefiting?

Glioblastoma multiforme (GBM) is the deadliest form of adult brain cancer. GBM develops when glial cells, which support and insulate nerve cells, develop mutations to alter gene activity. While efforts have been made to understand the molecular mechanisms driving glioblastoma and to develop novel therapeutic targets to treat the disease, patient survival has not improved over the past 70 years. It was previously discovered that the Daam2 protein plays a key role in promoting tumorigenesis by facilitating the degradation of a key tumor suppressor, von Hippel Landau (VHL). Preliminary studies showed that overexpression of Daam2 mutations in GBM patient-derived stem cells resulted in increased tumor proliferation in vitro and in vivo. Interestingly, five germline mutations have been found in Daam2 in 6 families with a history of familial glioma, but no causal relationship has been identified. This raised the questions: what role do these Daam2 variants play in tumorigenesis and how do they affect the interaction and degradation of VHL? To answer the latter question, we expressed wildtype Daam2 and the human variants (e.g., p.R414W, p.P555L) with VHL by transfecting plasmids into HEK293T cells. Cells were then harvested and a co-immunoprecipitation (Co-IP) was performed using the extracted protein lysates to pull down Daam2. Levels of VHL were assessed to determine protein-protein interactions between Daam2 variants and VHL. By understanding how Daam2 variants and VHL interact, potential targets can be pinpointed in these mechanistic pathways that could be exploited as therapeutic entry points to treat GBM.